It is generally known that the smoking of tobacco products, such as cigarettes, cigars, and pipe tobacco, presents serious health risks to the user and those subjected to second hand smoke. It is also known that the use of other forms of tobacco, such as chewing tobacco, can also result in serious health risks to the user.
Although the damaging effects of tobacco smoking are well known, most individuals with nicotine dependence have great difficulty in overcoming the dependence. The difficulty arises, in large part, due to the addictive nature of nicotine. Overcoming nicotine craving is the critical challenge for those attempting to conquer nicotine dependence. These cravings may arise in several ways. For instance, studies have shown that following a quit attempt, smokers report moderate levels of steady nicotine craving throughout the day. Those who more intensely crave nicotine are more likely to relapse and return to using tobacco. In addition to steady cravings, smokers also experience episodic, or acute, cravings. These acute cravings can be provoked by a variety of stimula, such as exposure to smoking related cues, seeing smoking paraphernalia or others smoking, or inhaling second hand smoke. Such episodic craving can also result in relapse if proper coping measures are not employed.
In recent years, Nicotine Replacement Therapies (NRTs) have been successfully commercialized as a means to reduce or quit smoking, chewing and other methods of tobacco usage. NRT is generally effective to temporarily replace some of the nicotine that is lost when a user quits using tobacco. Such commercial NRTs include nicotine gums (e.g. NICORETTE®) and transdermal nicotine patch systems (e.g. NICODERM®, NICOTROL®, PROSTEP® and HABITROL®). Generally, transdermal nicotine patches are useful for maintaining relatively steady blood level concentrations over time by providing the user with a substantially continuous infusion of nicotine while the patch is worn. Likewise, when used at regular intervals, nicotine gum can maintain relatively steady blood nicotine concentrations over time. Thus, both the nicotine patch and the nicotine gum can be effective against the steady nicotine craving experienced by an individual in the process of quitting tobacco usage. However, those individuals more prone to intense and acute nicotine cravings may desire more rapid, or intermittent, craving relief than typically provided by a transdermal nicotine patch.
In some circumstances, nicotine gum can be used to relieve the acute cravings experienced by the individual that is attempting to quit smoking or other tobacco use. For example, a single piece of gum may be self-administered by an individual in response to an acute nicotine craving. Such use of the nicotine gum typically results in an increase in blood nicotine levels to counteract the nicotine craving, however, the gum tends to release nicotine somewhat slowly in the oral cavity and may not provide relief as quickly as the individual would like. In addition, this intermittent gum use would not be as effective against the more constant nicotine cravings.
Nicotine lozenges are also commercially available and may be utilized in a similar manner to provide relief from acute nicotine cravings. Currently available nicotine lozenges include, for example, COMMIT®, STOPPERS®, NIQUITIN®, and NICOTINELL® brand lozenges. Like the nicotine gum, a user may self-administer the lozenge in response to a nicotine craving and the lozenge will slowly release nicotine in the oral cavity.
However, a limitation of both the gum and lozenge NRT product forms is that they each have an average oral retention time of about 20 minutes to obtain the maximum benefit. Thus, craving relief may not be as fast as the individual would like. Further, due to this required oral retention time, users may administer the gum or lozenges less frequently than is actually needed or recommended, possibly resulting in more frequent nicotine cravings. For example, an individual may continue to chew the nicotine gum long after the majority of the available nicotine active has been consumed and may not realize that the gum has been exhausted and nicotine cravings may then result.
Thus, while existing NRT means may have some utility in helping to cope with steady and acute tobacco cravings, there is still an ongoing need to provide faster and more effective craving relief, as well as to provide other more convenient product forms.
Nicotine has been incorporated into water soluble films which generally comprise highly hydrohilic polymers to dissolve in the oral cavity and release nicotine for buccal absorption. In order to achieve fast dissolution, the water-soluble polymers typtically employed in these films have high hydration rates and result in a very hygroscopic film. Due to the volatile nature of nicotine, however, films of this type generally result in compromised nicotine stability.
Several patents within the same patent family have issued to Zerbe et al. relating to mucoadhesive films. U.S. Pat. No. 5,948,430, reexamined at 90/005887, relates to a monolayer film formed from a mucoadhesive composition comprising: at least one water soluble polymer; a surfactant alone or in combination with at least one member selected from the group consisting of a polyalcohol and a plasticizer, or a polyalcohol and a plasticizer; at least one cosmetic or pharmaceutical ingredient and a flavoring agent; said film being one which rapidly softens and completely disintegrates in the oral environment and having dry film thickness which is suitable for application into the mouth without causing adverse feeling in the mouth. U.S. Pat. No. 6,709,671 relates to various monolayer films formed from a mucoadhesive composition comprising: at least one water soluble polymer; a surfactant, an active and additional components, such as a water-dispersible polymer. U.S. Pat. No. 6,177,096 relates to a composition comprising at least one water soluble polymer, at least one polyalcohol, and at least one active agent, wherein the composition has mucoadhesive properties. U.S. Pat. No. 6,284,264 relates to methods for releasing an active agent into the oral cavity by applying a mucoadhesive film comprising the active into the oral cavity of a person, allowing the mucoadhesive film to dissolve within the oral cavity and releasing the active into the oral cavity, more specifically releasing the active agent to the patient via the mucous membrane. U.S. Pat. No. 6,592,887 relates to the same method for releasing an active agent into the oral cavity but specifically requires that the active agent be nicotine. The disclosures of each of these patents contain examples of a dry film wherein nicotine salicylate is the pharmaceutical ingredient used, and where the composition also comprises hydroxypropylmethyl cellulose, polyvinylpyrrolidone, a flavoring agent and a colorant.
European Pat. No. Application EP1 008 343 A1 to Kyukyu Pharmaceutical Co., relates to a film preparation mainly comprising a drug, an edible polymer and a saccharide, which is rapidly soluble in the oral cavity.
PCT Application, WO 00/42992 relates to a dosage unit comprising a water-soluble hydrocolloid, mucosal surface coat-forming film, where the film includes an effective dose of an active agent. The film can be hydroxypropylmethyl cellulose polymer and the active agent can be nicotine. The film, on contact with the moist mucosal surface of the mouth, becomes a coating that adheres to the mucosal surface and then disintegrates and dissolves to release the active agent.
PCT Application WO 02/43657 discloses pullulan free edible film compositions comprising effective amounts of at least one film forming agent, at least one bulk filler agent and at least one plasticizing agent.
PCT Application WO 01/70194 to Warner Lambert Company 7 broadly relates to consumable films adapted to adhere and dissolve in the mouth of a consumer, wherein the film comprises at least one water soluble polymer, at least one active agent and at least one taste masking agent.
As far as the inventors of the instant invention are aware, the nicotine containing orally dissolving films described above, do not address the difficulty associated with effectively driving transbuccal absorption of nicotine and maintaining nicotine stability. Therefore, there remains a need for a rapidly dissolving oral film that effectively delivers a nicotine active to a user in a sufficient amount to reduce or eliminate the steady or acute nicotine cravings associated with quitting tobacco usage.